study of the efficacy and safety of nicotinamide in patients with diabetes mellitus type 2 and liver fibrosis (nicofib)

Conditions: Fatty Liver; Obesity; Diabete Type 2; Hepatic Fibrosis; NAFLD; Nicotinamide

Summary: the objective of this clinical trial, a pilot study, is to assess the impact of nicotinamide (nam) on individuals with hepatic fibrosis. the main question it aims to answer is: - to determine if the treatment with nam is able to arrest, or even reduce, the hepatic fibrosis. in addition, we also want to study the effect of nam on: * general parameters (weight, homa-ir, etc). * adiposity distribution (liver and body). * systemic inflammation. * thermogenic capacity of adipose tissue. * microbiota composition. researchers will compare nam to a placebo, to see if nam can arrest or revert hepatic fibrosis and its associated effects. participants will take either nam or placebo. the dosage will be 1.2g/m2 nam per day, for one year.

patients with a fibroscan \> 8 kpa will be offered to participate in this study. participants will receive either placebo or a nam dose adjusted to body weight. the duration of the treatment is 12 months. participants will be subjected to a total of 5 follow-up and/or control visits: visit 1 * physical examination(weight, height, bmi, waist circumference, neck circumference, blood pressure, and heart rate). * assessment of muscle status and risk of sarcopenia: grip strength, chair test. * basal electrocardiogram. * blood analysis. * bioelectrical impedance analysis. * liver ultrasound. * ultrasound of abdominal and preperitoneal fat. * musculoskeletal ultrasound. * nuclear magnetic resonance. * thermographic image. * food questionnaire (predimed). * international physical activity questionnaire (ipaq). * collection of blood, urine, and feces samples for storage in the biobank. visit 2. control visit (time month 1) * monitoring of adverse events (ae) and adverse reactions (ar). * electrocardiogram. * control blood analysis: sodium, potassium, liver biochemistry (ast, alt, bilirubin, ggt, fa), renal function (urea, creatinine, estimated glomerular filtration), and coagulation tests. * physical examination and measurement of vital signs. visit 3. follow-up visit (time month 3) * monitoring of ae and ar. * drug adherence questionnaire. * electrocardiogram. * blood analysis. * physical examination (weight, bmi, waist circumference, neck circumference, blood pressure, and heart rate). * collection of blood, urine, and feces samples for biobank. * collection of concomitant medication. * adherence to study treatment and dietary recommendations. visit 4. follow-up visit (time month 6) * monitoring of ae and ar. * drug adherence questionnaire. * electrocardiogram. * blood analysis. * physical examination (weight, bmi, waist circumference, neck circumference, blood pressure, and heart rate). * collection of blood, urine, and feces samples for biobank. * collection of concomitant medication. * adherence to study treatment and dietary recommendations. visit 5. control visit (time month 9). * monitoring of ae and ar. * drug adherence questionnaire. * electrocardiogram. * control blood analysis. * physical examination. * collection of concomitant medication. visit 6. final exploration (time month 12) * monitoring of ae and ar. * drug adherence questionnaire. * food questionnaire (predimed). * physical activity questionnaire (ipaq). * physical examination and measurement of vital signs (weight, bmi, waist circumference, neck circumference, blood pressure, and heart rate). * assessment of muscle status and risk of sarcopenia: fpm, chair test. * electrocardiogram. * blood analysis. * measurement of nam and derived metabolites in serum and urine. * nuclear magnetic resonance. * bioimpedance. * liver ultrasound. * ultrasound of abdominal and preperitoneal fat. * musculoskeletal ultrasound. * thermographic image. * fibroscan® with cap. * collection of blood, urine, and feces samples for biobank the safety of the participants will be assessed using a record of the aes and ars that could arise and their annotation in the edc, as well as a regular evaluation of liver, kidney, and heart function at baseline, 1, 3, 6, 9 and 12 months

Eligibility criteria:
inclusion criteria: * patients aged between 18 and 85 years. * diagnosis of non-alcoholic fatty liver disease (nafld) by their referring physicians (nafld defined as the presence of hepatic steatosis and in the absence of significant alcohol consumption, having excluded other liver diseases). * bmi between 30-40 kg/m2. * type 2 diabetes mellitus (t2dm) diagnosed by their referring physicians. * fibroscan® value greater than 9.2 kpa, obtained within the last 6 months prior to the start of the study. exclusion criteria: * patients with any medical condition or illness that, in the opinion of the investigator, could interfere with the study results and/or affect the patients' ability to participate or complete the study. * history of clinically significant heart disease (ejection fraction \ 2; clinically significant congenital or acquired valvular disease; symptomatic coronary artery disease such as myocardial infarction or angina, history of unstable arrhythmias, history of atrial fibrillation). * decreased renal function (estimated glomerular filtration rate \<45 ml/min/1.73 m2, calculated using the ckd-epi formula) at screening. * alcohol consumption exceeding 30 g/day in men or 20 g/day in women. * patients with significant impairment of liver function in the selection analysis defined as repeated values of ast, alt, and bilirubin \> 3 times the upper limit of normal. * positive for hepatitis b surface antigen or hepatitis c antibodies. * patients with hepatocellular carcinoma. * patients with liver cirrhosis (fibroscan® \> 18, compatible biopsy, or those who have experienced decompensations of cirrhosis). * patients diagnosed with human immunodeficiency virus (hiv). * patients with hypersensitivity or a history of severe allergies to nam or excipients used in the preparation of capsules (nam and placebo). * patients with iodinated contrast allergy. * history or evidence of an autoimmune disorder considered clinically significant by the investigator or requiring systemic, chronic use of systemic corticosteroids or other immunosuppressants. * patients on treatment with hepatotoxic drugs (amiodarone, immunosuppressants, art, antituberculosis drugs, corticosteroids, etc.). * patients consuming narcotic and psychotropic substances with hepatotoxic effects. * individuals with incapacitating diseases or cognitive impairment. * institutionalized patients or those without a fixed address. * principal investigator's discretion in case of indications of low adherence to the trial or follow-up visits. * individuals with a life expectancy of less than 12 months. * patients participating in another interventional clinical trial, excluding observational/natural history studies, at the start of the study or within the last 30 days before the start of the study. * previous use of vitamin b3 (nam), with abstinence required for at least 3 months before screening. * pregnant women as determined by a positive high-sensitivity serum or urine pregnancy test (minimum sensitivity of 25 iu/l or equivalent units of hcg) within 24 hours prior to screening, dosing, or completion of the study. women of childbearing potential (wocbp) will undergo a pregnancy test (serum or urine) 24 hours prior to screening, dosing, or completion of the study. such participants must use a highly effective contraceptive method, such as combined hormonal contraceptives or intrauterine device (iud), in accordance with the clinical trial facilitation group, throughout the entire study. * breastfeeding women. * patients undergoing treatment/supplementation with vitamin e. * patients receiving probiotics. * patients on the waiting list for bariatric surgery in the next 12 months. * patients undergoing treatment with drugs that may have an effect on the progression of liver disease. * drugs for the treatment of t2dm with effects on nafld (glp-1 analogs, thiazolidinediones such as pioglitazone) initiated within 6 months before the study start. * drugs for the treatment of t2dm with effects on intestinal microbiota (metformin, α-gi inhibitors, dpp-4 inhibitors, and sglt-2 inhibitors) initiated within 6 months before the study start. * patients who do not sign the informed consent. * patients with contraindications to the contrast agent to be used in imaging tests.

Keywords: nicotinamide fatty liver nafld diabetes type 2